Trial Outcomes & Findings for Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS (NCT NCT00573443)
NCT ID: NCT00573443
Last Updated: 2017-04-12
Results Overview
Episodes were counted each day and recorded in a daily diary. The outcome measure is the ratio of the episode rate over the 84-day treatment period to the rate during the baseline period, adjusted for study site, and underlying disease using longitudinal negative binomial regression.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
326 participants
Primary outcome timeframe
Baseline to Day 84
Results posted on
2017-04-12
Participant Flow
Subjects diagnosed with pseudobulbar affect (PBA) secondary to amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).
Participant milestones
| Measure |
AVP-923-30
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Double-Blind Phase
STARTED
|
110
|
107
|
109
|
|
Double-Blind Phase
Subjects With PBA Secondary to ALS
|
65
|
68
|
64
|
|
Double-Blind Phase
Subjects With PBA Secondary to MS
|
45
|
39
|
45
|
|
Double-Blind Phase
COMPLETED
|
101
|
88
|
94
|
|
Double-Blind Phase
NOT COMPLETED
|
9
|
19
|
15
|
|
Open-Label Extension Phase
STARTED
|
253
|
0
|
0
|
|
Open-Label Extension Phase
Subjects With PBA Secondary to ALS
|
146
|
0
|
0
|
|
Open-Label Extension Phase
Subjects With PBA Secondary to MS
|
107
|
0
|
0
|
|
Open-Label Extension Phase
COMPLETED
|
235
|
0
|
0
|
|
Open-Label Extension Phase
NOT COMPLETED
|
18
|
0
|
0
|
Reasons for withdrawal
| Measure |
AVP-923-30
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Double-Blind Phase
Lost to Follow-up
|
1
|
3
|
2
|
|
Double-Blind Phase
Exacerbation of MS symptoms
|
1
|
0
|
1
|
|
Double-Blind Phase
Adverse Event
|
1
|
5
|
0
|
|
Double-Blind Phase
Serious Adverse Event (AE)
|
2
|
3
|
1
|
|
Double-Blind Phase
Medication refusal due to AE
|
2
|
2
|
0
|
|
Double-Blind Phase
Withdrawal by Subject
|
2
|
2
|
7
|
|
Double-Blind Phase
Protocol Violation
|
0
|
2
|
1
|
|
Double-Blind Phase
Other
|
0
|
2
|
3
|
|
Open-Label Extension Phase
Lost to Follow-up
|
1
|
0
|
0
|
|
Open-Label Extension Phase
Exacerbation of MS symptoms
|
2
|
0
|
0
|
|
Open-Label Extension Phase
Adverse Event
|
3
|
0
|
0
|
|
Open-Label Extension Phase
Serious Adverse Event
|
5
|
0
|
0
|
|
Open-Label Extension Phase
Withdrawal by Subject
|
3
|
0
|
0
|
|
Open-Label Extension Phase
Protocol Violation
|
2
|
0
|
0
|
|
Open-Label Extension Phase
Other
|
2
|
0
|
0
|
Baseline Characteristics
Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS
Baseline characteristics by cohort
| Measure |
AVP-923-30
n=110 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=107 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=109 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Total
n=326 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
53.08 Years
STANDARD_DEVIATION 11.016 • n=5 Participants
|
50.81 Years
STANDARD_DEVIATION 11.114 • n=7 Participants
|
50.27 Years
STANDARD_DEVIATION 11.939 • n=5 Participants
|
51.39 Years
STANDARD_DEVIATION 11.356 • n=4 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
177 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
149 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Day 84Population: Intent-to-Treat (ITT) population - included all randomized subjects for the double-blind phase and all enrolled subjects for the open-label extension phase.
Episodes were counted each day and recorded in a daily diary. The outcome measure is the ratio of the episode rate over the 84-day treatment period to the rate during the baseline period, adjusted for study site, and underlying disease using longitudinal negative binomial regression.
Outcome measures
| Measure |
AVP-923-30
n=110 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=107 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=109 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
PBA Episode Rate Ratio (Post/Pre), Regression Adjusted
|
0.247 Unit-free (ratio of episodes/week)
95% Confidence Interval 3.447 • Interval 0.233 to 0.262
|
0.237 Unit-free (ratio of episodes/week)
95% Confidence Interval 6.048 • Interval 0.224 to 0.251
|
0.465 Unit-free (ratio of episodes/week)
95% Confidence Interval 6.642 • Interval 0.441 to 0.489
|
SECONDARY outcome
Timeframe: Baseline, Day 15, Day 29, Day 57, Day 84Population: ITT Population
Center for Neurologic Studies-Lability Scale (CNS-LS) is an instrument for the measurement of PBA that has been validated for the use in patients with ALS and MS. It is a 7-item self-report questionnaire that measures the frequency and severity of PBA episodes, including assessments of labile laughter and labile tearfulness,and provides a score for total PBA (total score can range from 7-35). The following 5-point scoring was used: 1=Applies never, 2=Applies rarely, 3=Applies occasionally, 4=Applies frequently, 5=Applies most of the time. A score of 13 or higher may suggest PBA, and the higher the score the more severe the episodes.
Outcome measures
| Measure |
AVP-923-30
n=110 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=107 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=109 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Mean Change From Baseline in CNS-LS Total Score by Visit
Day 15 (Visit2)
|
-6.77 Scores on a Scale
Standard Deviation 5.239
|
-6.27 Scores on a Scale
Standard Deviation 5.552
|
-4.58 Scores on a Scale
Standard Deviation 4.982
|
|
Mean Change From Baseline in CNS-LS Total Score by Visit
Day 29 (Visit 3)
|
-8.03 Scores on a Scale
Standard Deviation 5.591
|
-7.62 Scores on a Scale
Standard Deviation 5.421
|
-5.70 Scores on a Scale
Standard Deviation 5.034
|
|
Mean Change From Baseline in CNS-LS Total Score by Visit
Day 57 (Visit 4)
|
-8.59 Scores on a Scale
Standard Deviation 5.745
|
-8.89 Scores on a Scale
Standard Deviation 5.501
|
-5.66 Scores on a Scale
Standard Deviation 5.038
|
|
Mean Change From Baseline in CNS-LS Total Score by Visit
Day 84 (Visit 5)
|
-8.17 Scores on a Scale
Standard Deviation 6.104
|
-8.24 Scores on a Scale
Standard Deviation 6.126
|
-5.72 Scores on a Scale
Standard Deviation 5.280
|
SECONDARY outcome
Timeframe: Baseline to Day 84Population: Efficacy Evaluable (EE) Population - included all subjects who were protocol adherent, defined as those who completed the Day 84 visit or the end-of-study visit within 48 hours of a discontinuation, and who took as least 80% of their scheduled doses prior to discontinuation of the study medication.
The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Outcome measures
| Measure |
AVP-923-30
n=105 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=90 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=98 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)
Frequency Score
|
-1.68 Scores on a Scale
Standard Deviation 4.102
|
-3.09 Scores on a Scale
Standard Deviation 6.241
|
-1.25 Scores on a Scale
Standard Deviation 4.860
|
|
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)
Severity Score
|
-0.80 Scores on a Scale
Standard Deviation 3.109
|
-1.81 Scores on a Scale
Standard Deviation 4.206
|
-0.91 Scores on a Scale
Standard Deviation 4.026
|
SECONDARY outcome
Timeframe: Baseline to Day 84Population: ITT Population
The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Outcome measures
| Measure |
AVP-923-30
n=110 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=107 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=109 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)
Frequency Score
|
-1.62 Scores on a Scale
Standard Deviation 4.110
|
-2.56 Scores on a Scale
Standard Deviation 6.205
|
-1.33 Scores on a Scale
Standard Deviation 4.837
|
|
Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)
Severity Score
|
-0.74 Scores on a Scale
Standard Deviation 3.102
|
-1.59 Scores on a Scale
Standard Deviation 4.128
|
-0.98 Scores on a Scale
Standard Deviation 4.008
|
SECONDARY outcome
Timeframe: Baseline and Day 84Population: ITT Population
The SF-36 is designed to examine a person's perceived health status. The SF-36 includes one multi-item scale measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health. Answers to each question are scored and summed to produce raw scale scores for each health concept which are then transformed to a 0 - 100 scale, a high score defining a more favorable health state. An aggregate summary measure is calculated by averaging the scores from the eight health concepts.
Outcome measures
| Measure |
AVP-923-30
n=110 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=107 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=109 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Physical Functioning Scale
|
-0.90 Scores on a Scale
Standard Deviation 17.336
|
-5.30 Scores on a Scale
Standard Deviation 15.652
|
-4.05 Scores on a Scale
Standard Deviation 16.381
|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Role Physical Scale
|
3.47 Scores on a Scale
Standard Deviation 36.747
|
-4.26 Scores on a Scale
Standard Deviation 39.764
|
-1.75 Scores on a Scale
Standard Deviation 40.084
|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Bodily Pain Scale
|
4.09 Scores on a Scale
Standard Deviation 20.861
|
5.84 Scores on a Scale
Standard Deviation 20.437
|
-1.13 Scores on a Scale
Standard Deviation 21.782
|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
General Health Scale
|
-1.47 Scores on a Scale
Standard Deviation 17.273
|
-2.95 Scores on a Scale
Standard Deviation 16.266
|
-1.28 Scores on a Scale
Standard Deviation 15.824
|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Vitality Scale
|
-0.90 Scores on a Scale
Standard Deviation 17.336
|
-5.30 Scores on a Scale
Standard Deviation 15.652
|
-4.05 Scores on a Scale
Standard Deviation 16.381
|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Social Functioning Scale
|
9.34 Scores on a Scale
Standard Deviation 25.105
|
1.42 Scores on a Scale
Standard Deviation 28.577
|
-3.09 Scores on a Scale
Standard Deviation 28.908
|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Role Emotional Scale
|
11.55 Scores on a Scale
Standard Deviation 47.711
|
-1.81 Scores on a Scale
Standard Deviation 45.924
|
2.36 Scores on a Scale
Standard Deviation 45.984
|
|
Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category
Mental Health Scale
|
5.53 Scores on a Scale
Standard Deviation 17.067
|
3.09 Scores on a Scale
Standard Deviation 16.877
|
-0.28 Scores on a Scale
Standard Deviation 13.720
|
SECONDARY outcome
Timeframe: Baseline and Day 84Population: ITT Population
The BDI-II is a 21-item self report instrument intended to assess the existence and severity of symptoms of depression, summed to give a single score. The BDI-II uses a 4-point for each item ranging from 0 to 3. A total score of 0-13 is considered minimal range, 14 to 19 is mild, 20 to 28 is moderate, and 29 to 63 is severe.
Outcome measures
| Measure |
AVP-923-30
n=110 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=107 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=109 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score
|
-1.59 Scores on a Scale
Standard Deviation 5.294
|
-1.03 Scores on a Scale
Standard Deviation 5.183
|
-0.02 Scores on a Scale
Standard Deviation 6.320
|
SECONDARY outcome
Timeframe: Baseline, Day 15, Day 29, Day 57, Day 84Population: ITT Population - MS Subjects only
Subjects with MS were instructed to also record daily the pain they experienced using the PRS. After evaluating the subject's ability to comply with these requirements, the investigator determined if a caregiver should complete the study diary and assessments. Subjects rated their pain over the past 12 hours on a scale of 0 to 10 (0=none, 10=worst pain ever experienced).
Outcome measures
| Measure |
AVP-923-30
n=45 Participants
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week open-label extension (OLE) period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
AVP-923-20
n=39 Participants
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
Placebo
n=45 Participants
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period. Subjects who completed the DB period of this treatment arm could begin an optional 12 week OLE period taking AVP-923 capsule containing 30 mg DM and 10 mg Q twice daily.
|
|---|---|---|---|
|
Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects
|
-1.0 Scores on a Scale
Standard Deviation 2.39
|
-0.7 Scores on a Scale
Standard Deviation 1.84
|
-0.4 Scores on a Scale
Standard Deviation 2.61
|
Adverse Events
AVP-923-30 (Double-blind)
Serious events: 8 serious events
Other events: 66 other events
Deaths: 0 deaths
AVP-923-20 (Double-blind)
Serious events: 9 serious events
Other events: 65 other events
Deaths: 0 deaths
Placebo (Double-blind)
Serious events: 10 serious events
Other events: 63 other events
Deaths: 0 deaths
AVP-923-30 (Open Label)
Serious events: 14 serious events
Other events: 123 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AVP-923-30 (Double-blind)
n=110 participants at risk
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period.
|
AVP-923-20 (Double-blind)
n=107 participants at risk
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period.
|
Placebo (Double-blind)
n=109 participants at risk
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period.
|
AVP-923-30 (Open Label)
n=253 participants at risk
Optional 12-week Open Label phase for subjects who completed 12-week DB phase.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
2.7%
3/110
|
0.93%
1/107
|
0.92%
1/109
|
0.79%
2/253
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.91%
1/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.91%
1/110
|
0.00%
0/107
|
0.92%
1/109
|
0.40%
1/253
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY DEPRESSION
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATION
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
Respiratory, thoracic and mediastinal disorders
INCREASED BRONCHIAL SECRETION
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.91%
1/110
|
0.00%
0/107
|
1.8%
2/109
|
0.40%
1/253
|
|
Gastrointestinal disorders
STRIDOR
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Gastrointestinal disorders
RESPIRATORY DISORDER
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
Nervous system disorders
SYNCOPE
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Nervous system disorders
MUSCLE SPASTICITY
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Nervous system disorders
MULTIPLE SCLEROSIS
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Nervous system disorders
MULTIPLE SCLEROSIS RELAPSE
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.79%
2/253
|
|
Infections and infestations
UROSEPSIS
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
Infections and infestations
PNEUMONIA
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Infections and infestations
INFECTION
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
Infections and infestations
CATHETER RELATED INFECTION
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Infections and infestations
TOOTH INFECTION
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Infections and infestations
SKIN INFECTION
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Infections and infestations
POSTOPERATIVE WOUND INFECTION
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Infections and infestations
APPENDICITIS
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Injury, poisoning and procedural complications
POSTOPERATIVE RESPIRATORY DISTRESS
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Injury, poisoning and procedural complications
OVERDOSE
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Injury, poisoning and procedural complications
FEEDING TUBE COMPLICATION
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.40%
1/253
|
|
Injury, poisoning and procedural complications
COMPLICATION OF DEVICE INSERTION
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
Injury, poisoning and procedural complications
RADIUS FRACTURE
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Injury, poisoning and procedural complications
HAND FRACTURE
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Injury, poisoning and procedural complications
FACIAL BONES FRACTURE
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
0.00%
0/110
|
0.00%
0/107
|
1.8%
2/109
|
0.00%
0/253
|
|
Psychiatric disorders
SUICIDE ATTEMPT
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Psychiatric disorders
ANXIETY
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Psychiatric disorders
PSYCHOTIC DISORDER
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
|
Investigations
OXYGEN SATURATION DECREASED
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Investigations
CARDIAC ENZYMES INCREASED
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
General disorders
DISEASE PROGRESSION
|
0.00%
0/110
|
0.93%
1/107
|
0.92%
1/109
|
0.40%
1/253
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER
|
0.00%
0/110
|
0.00%
0/107
|
0.92%
1/109
|
0.00%
0/253
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/110
|
0.93%
1/107
|
0.00%
0/109
|
0.00%
0/253
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.91%
1/110
|
0.00%
0/107
|
0.00%
0/109
|
0.40%
1/253
|
Other adverse events
| Measure |
AVP-923-30 (Double-blind)
n=110 participants at risk
AVP-923 capsules containing 30 mg dextromethorphan (DM) and 10 mg quinidine (Q) taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week double-blind (DB) period.
|
AVP-923-20 (Double-blind)
n=107 participants at risk
AVP-923 capsules containing 20 mg DM and 10 mg Q taken orally once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period.
|
Placebo (Double-blind)
n=109 participants at risk
Capsules containing placebo once daily for 1 week and twice daily for 11 additional consecutive weeks for a 12 week DB period.
|
AVP-923-30 (Open Label)
n=253 participants at risk
Optional 12-week Open Label phase for subjects who completed 12-week DB phase.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
NAUSEA
|
12.7%
14/110
|
7.5%
8/107
|
9.2%
10/109
|
5.9%
15/253
|
|
Gastrointestinal disorders
DIARRHOEA
|
10.0%
11/110
|
13.1%
14/107
|
6.4%
7/109
|
0.00%
0/253
|
|
Gastrointestinal disorders
CONSTIPATION
|
6.4%
7/110
|
5.6%
6/107
|
8.3%
9/109
|
6.7%
17/253
|
|
Gastrointestinal disorders
DYSPHAGIA
|
3.6%
4/110
|
5.6%
6/107
|
1.8%
2/109
|
0.00%
0/253
|
|
Gastrointestinal disorders
DRY MOUTH
|
6.4%
7/110
|
1.9%
2/107
|
0.00%
0/109
|
0.00%
0/253
|
|
General disorders
FATIGUE
|
8.2%
9/110
|
10.3%
11/107
|
9.2%
10/109
|
11.9%
30/253
|
|
Infections and infestations
NASOPHARYNGITIS
|
8.2%
9/110
|
5.6%
6/107
|
7.3%
8/109
|
5.5%
14/253
|
|
Infections and infestations
URINARY TRACT INFECTION
|
7.3%
8/110
|
3.7%
4/107
|
2.8%
3/109
|
7.5%
19/253
|
|
Injury, poisoning and procedural complications
FALL
|
20.0%
22/110
|
13.1%
14/107
|
20.2%
22/109
|
15.8%
40/253
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
6.4%
7/110
|
2.8%
3/107
|
9.2%
10/109
|
0.00%
0/253
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
4.5%
5/110
|
1.9%
2/107
|
7.3%
8/109
|
5.5%
14/253
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
5.5%
6/110
|
4.7%
5/107
|
3.7%
4/109
|
6.7%
17/253
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/110
|
0.00%
0/107
|
0.00%
0/109
|
6.3%
16/253
|
|
Nervous system disorders
HEADACHE
|
13.6%
15/110
|
14.0%
15/107
|
15.6%
17/109
|
10.7%
27/253
|
|
Nervous system disorders
DIZZINESS
|
18.2%
20/110
|
10.3%
11/107
|
5.5%
6/109
|
6.7%
17/253
|
|
Nervous system disorders
SOMNOLENCE
|
10.0%
11/110
|
8.4%
9/107
|
9.2%
10/109
|
6.3%
16/253
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/110
|
0.93%
1/107
|
5.5%
6/109
|
0.00%
0/253
|
Additional Information
Nadine Knowles; Executive Director, Research & Development Operations
Avanir Pharmaceuticals
Phone: 1-949-268-8972
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60